Characterization of the immune landscape in healthy mouse prostate and during prostate cancer progression.

IF 6.5 2区医学 Q1 IMMUNOLOGY

Oncoimmunology Pub Date : 2025-12-01 Epub Date: 2025-09-26 DOI:10.1080/2162402X.2025.2562220

Despoina Pervizou, Joanna De Chiara, Lionel Spinelli, Maïa Nestor-Martin, Lionel Chasson, Kateryna Len-Tayon, Darya Yanushko, Frédéric Fiore, Marc Bajénoff, Bernard Malissen, Daniel Metzger, Gilles Laverny, Sandrine Henri

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Abstract

The immune landscape of healthy prostate and its alterations during prostate cancer (PCa) progression remain poorly characterized. Using scRNA-sequencing and multiparametric flow-cytometry analysis, we comprehensively characterized immune cells in wild-type and PTEN^(i)pe-/- mouse prostates, a model that closely recapitulates human PCa. PCa in PTEN^(i)pe-/- is marked by the recruitment of tumor-associated neutrophils (TANs), which represent the dominant immune cell population and resolved into eight distinct states, Trem2⁺ tumor-associated-macrophages (TAMs), and exhausted CD8⁺ T cells. Trem2⁺ TAMs differ from the three main resident macrophage populations in the healthy prostate, exhibiting a strong metabolic and immunosuppressive signature, likely driven by the MIF/HIF1A-signaling axis. This study provides the first detailed characterization of immune cells in the healthy mouse prostate and reveals changes in the immune landscape associated with prostate cancer progression.

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健康小鼠前列腺和前列腺癌进展过程中免疫景观的特征

健康前列腺的免疫景观及其在前列腺癌（PCa）进展过程中的改变仍然缺乏特征。利用scrna测序和多参数流式细胞术分析，我们全面表征了野生型和PTEN(i)pe-/-小鼠前列腺中的免疫细胞，PTEN(i)pe-/-小鼠前列腺是一种与人类PCa密切相关的模型。PTEN(i)pe-/-中的PCa以肿瘤相关中性粒细胞（TANs）的募集为标志，TANs代表了主要的免疫细胞群，并分解为8种不同的状态，Trem2+肿瘤相关巨噬细胞（TAMs）和耗尽的CD8+ T细胞。Trem2+ tam不同于健康前列腺中的三种主要常驻巨噬细胞群，表现出强烈的代谢和免疫抑制特征，可能是由MIF/ hif1a信号轴驱动的。这项研究首次提供了健康小鼠前列腺免疫细胞的详细特征，并揭示了与前列腺癌进展相关的免疫景观的变化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncoimmunology ONCOLOGYIMMUNOLOGY-IMMUNOLOGY

CiteScore

12.50

自引率

2.80%

发文量

276

审稿时长

24 weeks

期刊介绍： OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy. As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology. The journal covers a wide range of topics, including: -Basic and translational studies in immunology of both solid and hematological malignancies -Inflammation, innate and acquired immune responses against cancer -Mechanisms of cancer immunoediting and immune evasion -Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells -Immunological effects of conventional anticancer therapies.